Religiosity has been shown to be a resource for many adults with HIV, but may be expressed differently by sexual orientation. In a state-wide survey, 395 adults with HIV were assessed on a variety of medical and psychosocial measures. Factors were extracted for age, health status, disease duration, education, social support, mood, and religiosity and were specified in a structural equation model for 2 groups (i.e., homosexuals and heterosexuals), where religiosity was proposed to mediate the effects of age, education, and chronicity on the biopsychosocial outcomes of health, social support, and mood. All of the trimmed models fit the data well. For homosexuals (n = 165), religiosity was positively related to social support. For heterosexuals (n = 230), those who were older had higher levels of religiosity but religiosity did not mediate any of the biopsychosocial outcomes. Results from this structural equation modeling comparison study suggest that religiosity may facilitate certain positive biopsychosocial outcomes in different groups. © Taylor & Francis Group, LLC.